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14-3-3 Family of Proteins: Biological Implications, Molecular Interactions, and Potential Intervention in Cancer, Virus and Neurodegeneration Disorders

Low ZY, Yip AJW, Chan AML, Choo WS

J Cell Biochem, 2024 Jul;125(7):e30624.
PMID: 38946063 DOI: 10.1002/jcb.30624

The 14-3-3 family of proteins are highly conserved acidic eukaryotic proteins (25-32 kDa) abundantly present in the body. Through numerous binding partners, the 14-3-3 is responsible for many essential cellular pathways, such as cell cycle regulation and gene transcription control. Hence, its dysregulation has been linked to the onset of critical illnesses such as cancers, neurodegenerative diseases and viral infections. Interestingly, explorative studies have revealed an inverse correlation of 14-3-3 protein in cancer and neurodegenerative diseases, and the direct manipulation of 14-3-3 by virus to enhance infection capacity has dramatically extended its significance. Of these, COVID-19 has been linked to the 14-3-3 proteins by the interference of the SARS-CoV-2 nucleocapsid (N) protein during virion assembly. Given its predisposition towards multiple essential host signalling pathways, it is vital to understand the holistic interactions between the 14-3-3 protein to unravel its potential therapeutic unit in the future. As such, the general structure and properties of the 14-3-3 family of proteins, as well as their known biological functions and implications in cancer, neurodegeneration, and viruses, were covered in this review. Furthermore, the potential therapeutic target of 14-3-3 proteins in the associated diseases was discussed.

Matched MeSH terms: Virus Diseases/genetics; Virus Diseases/metabolism; Virus Diseases/virology
Abstracts of the 6th Asia Pacific Congress of Medical Virology. 7-10 December 2003. Kuala Lumpur, Malaysia

J Clin Virol, 2003 Dec;28 Suppl 1:S19-108.
PMID: 14725272
Matched MeSH terms: Virus Diseases*
Fulltext Can egg yolk antibodies terminate the CSBV infection in apiculture?

Li A, Wang Q, Huang Y, Hu L, Li S, Wang Q, et al.

Virus Res, 2023 Apr 15;328:199080.
PMID: 36882131 DOI: 10.1016/j.virusres.2023.199080

Chinese sacbrood virus (CSBV) is the most severe pathogen of Apis cerana, which leads to serious fatal diseases in bee colonies and eventual catastrophe for the Chinese beekeeping industry. Additionally, CSBV can potentially infect Apis mellifera by bridging the species barrier and significantly affect the productivity of the honey industry. Although several approaches, such as feeding royal jelly, traditional Chinese medicine, and double-stranded RNA treatments, have been employed to suppress CSBV infection, their practical applicabilities are constrained due to their poor effectiveness. In recent years, specific egg yolk antibodies (EYA) have been increasingly utilized in passive immunotherapy for infectious diseases without any side effects. According to both laboratory research and practical use, EYA have demonstrated superior protection for bees against CSBV infection. This review provided an in-depth analysis of the issues and drawbacks in this field in addition to provide a thorough summary of current advancements in CSBV studies. Some promising strategies for the synergistic study of EYA against CSBV, including the exploitation of novel antibody drugs, novel TCM monomer/formula determination, and development of nucleotide drugs, are also proposed in this review. Furthermore, the prospects for the future perspectives of EYA research and applications are presented. Collectively, EYA would terminate CSBV infection soon, as well as will provide scientific guidance and references to control and manage other viral infections in apiculture.

Matched MeSH terms: Virus Diseases*
Fulltext Acute viral myocarditis, four cases in three weeks

Sufarlan AW, Khalid BA

Med J Malaysia, 1989 Dec;44(4):334-40.
PMID: 2520044

Four cases of acute viral myocarditis were diagnosed within three weeks. The clinical features, electrocardiography, cardiac enzymes and other laboratory investigations are described.

Matched MeSH terms: Virus Diseases/diagnosis; Virus Diseases/enzymology; Virus Diseases/etiology*
Paediatric viral infections

Lam SK

Ann Acad Med Singap, 1987 Apr;16(2):250-1.
PMID: 3318653

Viral infections are probably the most important cause of childhood morbidity and mortality in the world. In many developing countries in South East Asia and the Western Pacific, priority health problems include acute respiratory infections, acute diarrhoeas and arboviral infections. Where studies have been carried out, there is no significant difference in the aetiological agents involved or in the manifestation of clinical childhood disease. Surveillance of these diseases have improved with the introduction of rapid viral diagnosis. The better understanding of the immunopathogenesis of many diseases have also encouraged research in this area and will lead to the better control and management of these diseases. However, the search for antivirals has been disappointing but fortunately new vaccines are on the horizon and the prospect for bringing some of these diseases under control through vaccination are bright.

Matched MeSH terms: Virus Diseases/complications; Virus Diseases/epidemiology*; Virus Diseases/therapy
International spread of virus diseases with special reference to Malaya

SMITH CE

Med J Malaya, 1956 Sep;11(1):63-9; discussion, 69-70.
PMID: 13399543
Matched MeSH terms: Virus Diseases/epidemiology*
Dengue virus infection and neurological manifestations: an update

Fong SL, Wong KT, Tan CT

Brain, 2024 Mar 01;147(3):830-838.
PMID: 38079534 DOI: 10.1093/brain/awad415

Dengue virus is a flavivirus transmitted by the mosquitoes, Aedes aegypti and Aedes albopictus. Dengue infection by all four serotypes (DEN 1 to 4) is endemic globally in regions with tropical and subtropical climates, with an estimated 100-400 million infections annually. Among those hospitalized, the mortality is about 1%. Neurological involvement has been reported to be about 5%. The spectrum of neurological manifestations spans both the peripheral and central nervous systems. These manifestations could possibly be categorized into those directly related to dengue infection, i.e. acute and chronic encephalitis, indirect complications leading to dengue encephalopathy, and post-infectious syndrome due to immune-mediated reactions, and manifestations with uncertain mechanisms, such as acute transverse myelitis, acute cerebellitis and myositis. The rising trend in global dengue incidence calls for attention to a more explicit definition of each neurological manifestation for more accurate epidemiological data. The actual global burden of dengue infection with neurological manifestation is essential for future planning and execution of strategies, especially in the development of effective antivirals and vaccines against the dengue virus. In this article, we discuss the recent findings of different spectrums of neurological manifestations in dengue infection and provide an update on antiviral and vaccine development and their challenges.

Matched MeSH terms: Virus Diseases*
Tick-borne viruses: a review from the perspective of therapeutic approaches

Lani R, Moghaddam E, Haghani A, Chang LY, AbuBakar S, Zandi K

Ticks Tick Borne Dis, 2014 Sep;5(5):457-65.
PMID: 24907187 DOI: 10.1016/j.ttbdis.2014.04.001

Several important human diseases worldwide are caused by tick-borne viruses. These diseases have become important public health concerns in recent years. The tick-borne viruses that cause diseases in humans mainly belong to 3 families: Bunyaviridae, Flaviviridae, and Reoviridae. In this review, we focus on therapeutic approaches for several of the more important tick-borne viruses from these 3 families. These viruses are Crimean-Congo hemorrhagic fever virus (CCHF) and the newly discovered tick-borne phleboviruses, known as thrombocytopenia syndromevirus (SFTSV), Heartland virus and Bhanja virus from the family Bunyaviridae, tick-borne encephalitis virus (TBEV), Powassan virus (POWV), Louping-ill virus (LIV), Omsk hemorrhagic fever virus (OHFV), Kyasanur Forest disease virus (KFDV), and Alkhurma hemorrhagic fever virus (AHFV) from the Flaviviridae family. To date, there is no effective antiviral drug available against most of these tick-borne viruses. Although there is common usage of antiviral drugs such as ribavirin for CCHF treatment in some countries, there are concerns that ribavirin may not be as effective as once thought against CCHF. Herein, we discuss also the availability of vaccines for the control of these viral infections. The lack of treatment and prevention approaches for these viruses is highlighted, and we hope that this review may increase public health awareness with regard to the threat posed by this group of viruses.

Matched MeSH terms: Virus Diseases/transmission*; Virus Diseases/virology
Fulltext Viruses join the circular RNA world

Tan KE, Lim YY

FEBS J, 2021 08;288(15):4488-4502.
PMID: 33236482 DOI: 10.1111/febs.15639

Circular RNAs (circRNAs) are a recently discovered class of noncoding RNAs found in many species across the eukaryotic kingdom. These intriguing RNA species are formed through a unique mechanism that is known as back splicing in which the 5' and 3' termini are covalently joined. Recent research has revealed that viruses also encode a repertoire of circRNAs. Some of these viral circRNAs are abundantly expressed and are reported to play a role in disease pathogenesis. A growing number of studies also indicate that host circRNAs are involved in immune responses against virus infections with either an antiviral or proviral role. In this review, we briefly introduce circRNA, its biogenesis, and mechanism of action. We go on to summarize the latest research on the expression, regulation, and functions of viral and host-encoded circRNAs during the host-virus interaction, with the aim of highlighting the potential of viral and host circRNAs as a suitable target for diagnostic biomarker development and therapeutic treatment of viral-associated diseases. We conclude by discussing the current limitations in knowledge and significance of elucidating the roles of circRNAs in host-virus interactions, as well as future directions for this emerging field.

Matched MeSH terms: Virus Diseases/genetics*; Virus Diseases/virology
Immunization in virus disease

Tan DS

Med J Malaya, 1965 Sep;20(1):19-28.
PMID: 4221407
Matched MeSH terms: Virus Diseases/drug therapy*; Virus Diseases/immunology*
Fulltext T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses

Saeidi A, Zandi K, Cheok YY, Saeidi H, Wong WF, Lee CYQ, et al.

Front Immunol, 2018;9:2569.
PMID: 30473697 DOI: 10.3389/fimmu.2018.02569

T-cell exhaustion is a phenomenon of dysfunction or physical elimination of antigen-specific T cells reported in human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections as well as cancer. Exhaustion appears to be often restricted to CD8+ T cells responses in the literature, although CD4+ T cells have also been reported to be functionally exhausted in certain chronic infections. Although our understanding of the molecular mechanisms associated with the transcriptional regulation of T-cell exhaustion is advancing, it is imperative to also explore the central mechanisms that control the altered expression patterns. Targeting metabolic dysfunctions with mitochondrion-targeted antioxidants are also expected to improve the antiviral functions of exhausted virus-specific CD8+ T cells. In addition, it is crucial to consider the contributions of mitochondrial biogenesis on T-cell exhaustion and how mitochondrial metabolism of T cells could be targeted whilst treating chronic viral infections. Here, we review the current understanding of cardinal features of T-cell exhaustion in chronic infections, and have attempted to focus on recent discoveries, potential strategies to reverse exhaustion and reinvigorate optimal protective immune responses in the host.

Matched MeSH terms: Virus Diseases/immunology*; Virus Diseases/virology
Oral manifestations of microbial diseases

Singh G, Krishnan S

Med J Malaysia, 1978 Mar;32(3):232-5.
PMID: 683048
Matched MeSH terms: Virus Diseases/complications*
The uses of gamma globulin in the prevention of virus diseases

Tan DS

Med J Malaya, 1972 Dec;27(2):129-33.
PMID: 4123039
Matched MeSH terms: Virus Diseases/prevention & control*
A note on the laboratory diagnosis of virus and rickettsial diseases

SMITH CE

Med J Malaya, 1954 Sep;9(1):72-6.
PMID: 13213455
Matched MeSH terms: Virus Diseases/diagnosis*
A review of virus infections of the respiratory tract

Tan DS

Med J Malaya, 1965 Mar;19(3):201-12.
PMID: 4220472
Matched MeSH terms: Virus Diseases*
The clinical utility of CD163 in viral diseases

Yap YJ, Wong PF, AbuBakar S, Sam SS, Shunmugarajoo A, Soh YH, et al.

Clin Chim Acta, 2023 Feb 15;541:117243.
PMID: 36740088 DOI: 10.1016/j.cca.2023.117243

Macrophage activation and hypercytokinemia are notable presentations in certain viral infections leading to severe disease and poor prognosis. Viral infections can cause macrophage polarization into the pro-inflammatory M1 or anti-inflammatory M2 phenotype. Activated M1 macrophages usually restrict viral replication whereas activated M2 macrophages suppress inflammation and promote tissue repair. In response to inflammatory stimuli, macrophages polarize to the M2 phenotype expressing hemoglobin scavenger CD163 surface receptor. The CD163 receptor is shed as the soluble form, sCD163, into plasma or tissue fluids. sCD163 causes detoxification of pro-oxidative hemoglobin which produces anti-inflammatory metabolites that promote the resolution of inflammation. Hence, increased CD163 expression in tissues and elevated circulatory levels of sCD163 have been associated with acute and chronic inflammatory diseases. CD163 and other macrophage activation markers have been commonly included in the investigation of disease pathogenesis and progression. This review provides an overview of the involvement of CD163 in viral diseases. The clinical utility of CD163 in viral disease diagnosis, progression, prognosis and treatment evaluation is discussed.

Matched MeSH terms: Virus Diseases*
Fulltext Cross-sectional study of influenza trends and costs in Malaysia between 2016 and 2018

Wan Puteh SE, Aazmi MS, Aziz MN, Kamarudin N', Sam JI, Thayan R, et al.

PLoS One, 2024;19(3):e0301068.
PMID: 38517867 DOI: 10.1371/journal.pone.0301068

BACKGROUND AND OBJECTIVES: While influenza circulates year-round in Malaysia, research data on its incidence is scarce. Yet, this information is vital to the improvement of public health through evidence-based policies. In this cross-sectional study, we aimed to determine the trends and financial costs of influenza.
METHODS: Data for the years 2016 through 2018 were gathered retrospectively from several sources. These were existing Ministry of Health (MOH) influenza sentinel sites data, two teaching hospitals, and two private medical institutions in the Klang Valley, Malaysia. Expert consensus determined the final estimates of burden for laboratory-confirmed influenza-like illness (ILI) and severe acute respiratory infection (SARI). Economic burden was estimated separately using secondary data supplemented by MOH casemix costing.
RESULTS: Altogether, data for 11,652 cases of ILI and 5,764 cases of SARI were extracted. The influenza B subtype was found to be predominant in 2016, while influenza A was more prevalent in 2017 and 2018. The distribution timeline revealed that the highest frequency of cases occurred in March and April of all three years. The costs of influenza amounted to MYR 310.9 million over the full three-year period.
CONCLUSIONS: The study provides valuable insights into the dynamic landscape of influenza in Malaysia. The findings reveal a consistent year-round presence of influenza with irregular seasonal peaks, including a notable influenza A epidemic in 2017 and consistent surges in influenza B incidence during March across three years. These findings underscore the significance of continuous monitoring influenza subtypes for informed healthcare strategies as well as advocate for the integration of influenza vaccination into Malaysia's national immunization program, enhancing overall pandemic preparedness.

Matched MeSH terms: Virus Diseases*
[Emergence of new viruses in Asia: is climate change involved?]

Chastel C

Med Mal Infect, 2004 Nov;34(11):499-505.
PMID: 15620053

Tropical Africa is not the only area where deadly viruses have recently emerged. In South-East Asia severe epidemics of dengue hemorrhagic fever started in 1954 and flu pandemics have originated from China such as the Asian flu (H2N2) in 1957, the Hong-Kong flu (H3N2) in 1968, and the Russian flu (H1N1) in 1977. However, it is especially during the last ten years that very dangerous viruses for mankind have repeatedly developed in Asia, with the occurrence of Alkhurma hemorrhagic fever in Saudi Arabia (1995), avian flu (H5N1) in Hong-Kong (1997), Nipah virus encephalitis in Malaysia (1998,) and, above all, the SARS pandemic fever from Southern China (2002). The evolution of these viral diseases was probably not directly affected by climate change. In fact, their emergential success may be better explained by the development of large industry poultry flocks increasing the risks of epizootics, dietary habits, economic and demographic constraints, and negligence in the surveillance and reporting of the first cases.

Matched MeSH terms: Virus Diseases/classification*; Virus Diseases/epidemiology; Virus Diseases/transmission
Fulltext The multifarious roles of heterogeneous ribonucleoprotein A1 in viral infections

Kaur R, Lal SK

Rev Med Virol, 2020 03;30(2):e2097.
PMID: 31989716 DOI: 10.1002/rmv.2097

Viruses are obligate parasites known to interact with a wide variety of host proteins at different stages of infection. Current antiviral treatments target viral proteins and may be compromised due to the emergence of drug resistant viral strains. Targeting viral-host interactions is now gaining recognition as an alternative approach against viral infections. Recent research has revealed that heterogeneous ribonucleoprotein A1, an RNA-binding protein, plays an essential functional and regulatory role in the life cycle of many viruses. In this review, we summarize the interactions between heterogeneous ribonucleoprotein A1 (hnRNPA1) and multiple viral proteins during the life cycle of RNA and DNA viruses. hnRNPA1 protein levels are modulated differently, in different viruses, which further dictates its stability, function, and intracellular localization. Multiple reports have emphasized that in Sindbis virus, enteroviruses, porcine endemic diarrhea virus, and rhinovirus infection, hnRNPA1 enhances viral replication and survival. However, in others like hepatitis C virus and human T-cell lymphotropic virus, it exerts a protective response. The involvement of hnRNPA1 in viral infections highlights its importance as a central regulator of host and viral gene expression. Understanding the nature of these interactions will increase our understanding of specific viral infections and pathogenesis and eventually aid in the development of novel and robust antiviral intervention strategies.

Matched MeSH terms: Virus Diseases/genetics; Virus Diseases/metabolism*; Virus Diseases/virology*
Pathogenic viruses associated with bats of Malaysia

Balinu CP, Diam S, Chua TH

Trop Biomed, 2024 Sep 01;41(3):230-240.
PMID: 39548775 DOI: 10.47665/tb.41.3.001

Numerous human diseases, including those caused by viruses like Nipah virus and SARS-CoV, can be traced back to bats as their origin. Malaysia, notably Sabah and Sarawak in Borneo Island, is home to a rich diversity of bats that serve as hosts for various viruses. This comprehensive review represents the inaugural exploration of viruses found in Malaysian bats, as documented in scientific journals. It also encompasses documented instances of bat virus-related disease outbreaks in Malaysia up to the present day, along with an analysis of the risk factors associated with virus spillover events. Furthermore, this review offers insights into prospective research areas of significance and suggests potential mitigation strategies.

Matched MeSH terms: Virus Diseases/epidemiology; Virus Diseases/veterinary; Virus Diseases/virology

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